The mechanism of thyroid hormone entry into cells is under study, utilizing intact rat skeletal muscle, monolayer cell cultures of rat myocytes and human hepatocarcinoma cells, and an artificial membrane composed of dipalmitoyl phosphatidyl chokine (DPPC). Kinetics of thyroxine (T4) and triiodothyronine (T3) binding to DPPC vesicles showed more rapid entry of hormone when the lipid was in the liquid-crystal phase compared to the gel phase (T1/2 10 to 13 sec compared to 36 to 55 sec). The greater lipophilicity of T4 compared to T3 results in faster uptake of T4 when the lipid is in the gel phase. In the intact skeletal muscle as well as in cultured hepatic and skeletal muscle cells, about that presumably accounts for at least part of the entry of hormone into cells in vivo.